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Biomedical subjects

M Tomonaga

Publications and source records attributed to M Tomonaga.

At least 19 recordsLinked to original sources

Frequency of eosinophilia in adult T-cell leukemia/lymphoma.

Cases of adult T-cell leukemia/lymphoma (ATLL) display several peculiar clinical features, including skin rash, hypercalcemia, and an increase in the absolute neutrophil count. The patients rarely have pronounced eosinophilia. In this study, the eosinophilia observed in lymphoproliferative disorders of 62 patients with ATLL, 27 with T-cell lymphoma (TL), and 19 with B-cell lymphoma (BL) was investigated. The incidence of eosinophilia (greater than or equal to 570/microliters) was higher in patients with ATLL than in patients with TL or BL. Thirteen patients with ATLL (21.0%), 3 with TL (11.1%), and 2 with BL (10.5%) had eosinophilia. Of these patients, three with ATLL and one with TL who had a pathologic diagnosis of immunoblastic lymphadenopathy (IBL) showed pronounced eosinophilia up to 10,934/microliters. Because the number of eosinophils in the peripheral blood of these patients correlated both with the number of ATLL cells and the degree of lymphadenopathy and because this fluctuated with chemotherapy, it seems likely that the secretion of some lymphokines by the lymphoma cells is responsible for the eosinophilia.

Antineoplastic Combined Chemotherapy Protocols

Dementia in cerebral amyloid angiopathy: a clinicopathological study.

Dementia is in addition to cerebral haemorrhage major symptom of cerebral amyloid angiopathy (CAa). In order to explore the pathological basis for dementia in CAa-related conditions, we made a clinicopathological analysis of CAa, with special attention to dementia. Among 150 patients (mean age 78.6 years) with autopsy-proven intracranial haemorrhage in Tokyo Metropolitan Geriatric Medical Center, CAa with cerebral haemorrhage accounted for 8.0% (12 cases), associated with hypertension and metastatic brain tumour. Among 38 patients with lobar haemorrhage, CAa represented the second most common cause (21.1%) of intracranial haemorrhage after hypertension. A total of 20 patients with CAa (mean age 82.5 years) were studies clinically and pathologically. Hypertension was present in 50%. Thirteen had a history of stroke and others had either ill-defined or no strokes. The average number of strokes 2.9. Fifteen patients (75%) had dementia. Based on the clinicopathological grounds for dementia, CAa-related conditions could be divided into three subtypes: "haemorrhagic", "dementia-haemorrhagic" and "dementia" type. Haemorrhagic type (30%, 6 cases) showed multiple recurrent lobar haemorrhages caused by CAa. Hypertension was present in only 1 patient. The incidence of senile plaques and neurofibrillary tangles was generally correlated with age. Only 1 patient had dementia. The dementia-haemorrhagic type (40%, 8 patients) had recurrent strokes with cerebral haemorrhage after preceding dementia. There were two different neuropathological subsets: CAa with atypical senile dementia of Alzheimer type (SDAT) and CAa with diffuse leucoencephalopathy. Patients with CAa with atypical SDAT had multiple cerebral haemorrhages caused by CAa combined with atypical Alzheimer-type pathology. Patients with CAa with diffuse leucoencephalopathy had cerebral haemorrhages in combination with diffuse white matter damage like Binswanger's subcortical vascular encephalopathy (BSVE). The incidence of senile changes correlated with age. Patients with the dementia type (30%, 6 patients) showed progressive dementia with or without haemorrhage. All had hypertension. They had a combined condition of Alzheimer-type pathology with conspicuous CAa with BSVE. Dementia in CAa-related conditions may be responsible for multiple factors including not Alzheimer-type degeneration, but also diffuse leucoencephalopathy like Binswanger's disease. We also found an asymptomatic type, an ischaemic type, a vasculitis type and an hereditary type in this condition.

Aged

Electronmicroscopic observation of amyloid deposits in the vascular walls of the choroid plexus in systemic amyloidosis.

This report concerns an ultrastructural study of the vessels of the choroid plexus in 3 cases of systemic amyloidosis, sections of formalin-fixed brains being used. Small-sized arteries and arterioles were mainly affected by deposition of amyloid fibrils. In the arterioles, the amyloid fibrils were often so densely accumulated that they separated individual smooth muscle cells of the media and reached the subendothelial region. The basal surface of the endothelium of such vessels showed frequent invaginations filled with amyloid tufts; some of the tufts displaced the thin cytoplasm of the endothelial cells toward the lumen. Occasionally, tufts of amyloid fibrils were found to be exposed to and to float in the vascular lumen. These observations were made only in severely amyloid-laden vessels. Among the several possibilities regarding the tuft-endothelial relationship, the transendothelial transport of amyloid tufts is most likely, but the possibility of intraendothelial processing of amyloid precursor proteins and their secretion to form fibrils extracellularly cannot be excluded.

Adult

Chromosome 11 rearrangement at band 11q21 in a patient with essential thrombocythemia.

A case of essential thrombocythemia with a partial deletion of the long arm of chromosome 11, del(11)(q21) as a sole chromosomal anomaly is reported. Rearrangement of chromosome 11 at band 11q21 has been reported in six patients with chronic myeloproliferative disorders: four with post-polycythemic myelofibrosis, one with myelofibrosis with myeloid metaplasia, and one with Ph+ chronic myeloid leukemia in blastic phase. Except for the last patient, all patients had been treated with 32P and/or an alkylating agent prior to cytogenetic examination. This is the first report of the 11q21 abnormality in essential thrombocythemia seen at diagnosis.

Adult

Perception of complex geometric figures in chimpanzees (Pan troglodytes) and humans (Homo sapiens): analyses of visual similarity on the basis of choice reaction time.

In a conditional-discrimination task (matching-to-sample), we assessed similarities among figures consisting of 2 elemental figures through the choice reaction time, nonmetric multidimensional scaling, and hierarchical cluster analysis data from chimpanzees (Pan troglodytes) and humans (Homo sapiens). Humans also rated similarities among figures. The results of the 3 experiments clearly indicated that the reaction time data obtained from chimpanzees' performances were useful measures of the similarities among figures. The results suggested that chimpanzees and humans perceived the complex figures similarly. The outer-contour elements were perceived most dominantly by both species, and the straight-line elements were perceived least dominantly. Both species showed the same perceptual hierarchy or dominance among perceptual categories, as determined by the similarity of simple elements, on the basis of transformational invariances.

Adult

Remission with morphological myelodysplasia in de novo acute myeloid leukaemia: implications for early relapse.

Myelodysplastic features of remission bone marrow were investigated in 46 adults with de novo acute myeloid leukaemia (AML) according to the FAB morphological criteria for myelodysplastic syndromes (MDS). Compared with a group of 18 patients with the common type of acute lymphoblastic leukaemia in remission, micromegakaryocytes (30.4% v. 5.6%, P less than 0.05), multi-separated nuclear megakaryocytes (45.7% v. 0%, P less than 0.01), degranulated neutrophils (39.1% v. 5.6%, P less than 0.05), and neutrophils with hyposegmented nuclei (34.8% v. 0%, P less than 0.01) were significantly more common in the AML patients. In contrast, dyserythropoietic changes had a similar incidence in both groups. When compared with the clinical features at initial diagnosis in AML cases, the dysmegakaryocytic changes in remission marrow were found to be significantly more frequent in patients with monocytic involvement (mainly M4) or trilineage myelodysplasia (T-MDS AML). Disease-free survival was significantly shorter in patients with micromegakaryocytes (P less than 0.05) or neutrophils with hypogsegmented nuclei (P less than 0.05) than in those without these features. Overall survival was also significantly shorter in patients with micromegakaryocytes (P less than 0.05). These findings may help in developing new strategies for the post-remission therapy of AML, and also suggest that myelodysplastic changes in the remission marrow of de novo AML patients may be related to haematopoietic recovery by a preleukaemic clone which eventually leads to early leukaemic relapse. Dysplastic marrow, however, was not necessarily associated with peripheral pancytopenia in the present series, warranting basic research on such putative clonal remissions.

Acute Disease

[Infectious complications in patients with adult T-cell leukemia].

Between January, 1982, and January, 1992, a total of 112 patients with adult T-cell leukemia (ATL) and 109 patients with non-Hodgkin's lymphoma (NHL) were admitted to our hospital. They were studied for their infectious complications. Infectious complications were seen in 90 patients (80.4%) with ATL, and 51 patients (46.8%) with NHL (p < 0.001). Documented infections were seen in 70 patients (62.5%) with ATL, and 30 patients (27.5%) with NHL (p < 0.001). Pneumonia (p < 0.005), skin infections (p < 0.05), Pneumocystis carinii pneumonia (p < 0.05), fungal infections (p < 0.05), cytomegalovirus infections (p < 0.05) and herpes simplex virus infections (p < 0.01) were identified infections at high risk for patients with ATL. Tuberculosis, listeriosis and salmonella infections were seen only in patients with ATL.

Adolescent

A case of beta-thalassemia with a C----T substitution at position 654 of the second intervening sequence of the beta-globin gene.

A 26-year-old Chinese-Malaysian female patient with beta-thalassemia is presented. The main hematological values found in this patient were as follows: 1) normocytic hypochromic anemia (RBC 444 x 10(4)/microliters, Hb 11.8 g/dl) with marked anisopoikilocytosis, 2) erythroid hyperplasia, and 3) increased HbF (HbA 41.4%, HbA2 2.9%, HbF 48.9%). DNA obtained from peripheral leukocytes was analyzed using dot blot hybridization of the polymerase chain reaction (PCR)-amplified DNA with allele-specific oligonucleotide probes. A C----T substitution at position 654 of the second intervening sequence (IVS-2) was detected in her beta-globin clone.

Adult

[Clinicopathological evaluation of EVAL embolization in arteriovenous malformations].

The clinical and pathological aspects of two large arteriovenous malformations which were removed totally after preoperative embolization using ethylene vinyl alcohol copolymer (EVAL) were studied. The material, which is not adhesive, is handled easily during the procedure of embolization. However, it involves some risks because it might migrate to and occlude the normal branches of the brain and pass through the nidus to the venous system. Histopathological study of AVM nidus which was removed showed embolic materials within the vessels and inflammatory reaction of the vessel wall and its surrounding tissue. There were patchy hemorrhages within the AVM nidus and its surrounding brain tissue. Recanalization was also found within the occluded vessels. These findings suggest that preoperative embolization has some risk of causing intracerebral hemorrhage after the embolization. AVM should be removed surgically as a radical treatment if the patient is able to tolerate the operation.

Adolescent

Randomized study of individualized induction therapy with or without VCR, and of maintenance of 4 or 12 courses in adult AML: JALSG-AML87. Japan Adult Leukemia Study Group (JALSG).

We asked 2 questions in this study. First was the additional effect of VCR in induction therapy, and the second was the duration of maintenance therapy. Adult AML were treated by an individualized response-oriented induction therapy with behenoyl Ara-C 200 mg/m2 daily + 6MP 70 mg/m2 daily + prednisolone 40 mg/m2 on days 1-4 + DNA 40 mg/m2 on days 1-3 and additionally on days 7, 8, 11, 12 (for M3, DNR 50 mg/m2 daily) (BHAC-DMP) until bone marrow became severely hypoplastic with less than 5% of blasts. Patients were randomized to BHAC-DMP or BHAC-DMP + VCR 0.35 mg/m2 on days 1-4. After obtaining CR, 3 courses of intensive consolidation therapy were given together with I.T. MTX+Ara-C+PSL. Maintenance intensification therapy was randomized to either 4 or 12 courses given every 2 months. Patients of age greater than or equal to 60 received about 2/3 reduced doses. From June 1987 to Sept. 1989, 265 consecutive adult AML were registered from 19 institutions and 258 were evaluable. Age ranged from 15 to 79 (med., 48). Out of 258, 200 (77.5%) achieved CR (80% in 209 of age less than 60 and 65% in 49 of age greater than or equal to 60). Unexpectedly, addition of VCR reduced the high CR rate of BHAC-DMP significantly (84% to 70%, p = 0.007). At the median follow-up of 37 mo., overall survival is 37%, and event-free survival (EVS) 27%. Survival, continuing CR and disease-free survival (DFS) rates of 200 CR cases are 45%, 40% and 35%, respectively. Patients received 12 courses of maintenance therapy showed better DFS (P = 0.0555). The VCR group had significantly worse EFS. By multivariate analysis, significant prognostic factors for the achievement of CR were age less than 60, PS 0-2 and no addition of VCR. Significant factors for longer DFS were induction of CR by one course, FAB M3 or M5 and age less than 50. The present multi-institutional study confirmed the high CR rates of the response-oriented individualized therapy reported from several centers in Japan, but failed to support an additional effect of VCR reported from one center.

Acute Disease

[Efficacy of individual smoking cessation instructions for general smokers among clients of a health center].

Smoking cessation instruction for individuals using a standardized smoking cessation manual and a handout developed by the authors was studied in a controlled trial among employees who visited a health center for Industrial Safety and Health Law mandated annual health examinations. Smokers in the study group were given 5-10 minutes smoking cessation instruction mainly by public health nurses and nutritionists following the above-mentioned manual and using the handouts. Subjects in both groups were interviewed by telephone to assess changes in smoking habits one month after the first contact. Smoking clients who came on Friday (132) and on Monday (93) were assigned to study and control groups, respectively. One hundred and nineteen members (90.2%) of the study group and 88 (94.6%) of the control group were successfully followed until one month after the initial contact. Seven subjects in the study group were not smoking one month after the instruction, while no one gave up smoking in the control group (p less than 0.05). It was confirmed by telephone survey that 6 of the 7 subjects who were not smoking at one month were still maintaining abstinence from smoking one year after the instruction. Smokers who did not stop smoking reported a reduction in their smoking dose in the study group. Lighter smokers reacted more readily to instruction than did heavier smokers and the knowledge level of subjects was positively associated with the success rate.

Adolescent

[Epidemiology of HTLV-I carriers in Hirado Island and virological and immunological investigation of HTLV-I associated pulmonary disease].

Adult T-cell leukemia (ATL) is endemic in Kyushu. Our study at Hirado island in Nagasaki prefecture revealed a higher incidence (35.9%) of HTLV-I carriers in villages with fishing than in those without (16.5%). HTLV-I carriers showed a higher incidence of abnormal findings on chest roentgenogram (21.7%) than non-carriers (16.5%), but most were lesions of old pulmonary tuberculosis and pleural thickening. Virological and immunological investigations were performed for 10 HTLV-I carriers, 3 patients with HTLV-I associated myelopathy (HAM), and 3 patients with ATL to determine the presence of HTLV-I associated pulmonary disease. In HAM patients, there were high titers of anti HTLV-I antibody, positive IgA reaction to HTLV-I, and an increase in interleukin-2 receptor (IL-2)-positive T-cells in the peripheral blood; and lymphocytosis and an increase in IL-2-positive T-cells in the bronchoalveolar lavage fluid (BALF). Virological examination showed the presence of pX gene and tax1/rex1 mRNA in the peripheral blood and BALF. Similar immunological and virological findings in 2 of 10 carriers suggested the presence of HTLV-I associated pulmonary disease.

Aged

Rapid appearance of beta-amyloid precursor protein immunoreactivity in damaged axons and reactive glial cells in rat brain following needle stab injury.

Brains of rats that had received needle stab wounds were examined sequentially for 72 h by immunohistochemistry using antibodies to beta-amyloid precursor protein (APP). Immunoreactivity appeared 0.5 h after the injury in axons adjacent to the needle tract, becoming stronger over 15 h in neighboring swollen axons. APP-immunoreactive glial cells appeared 6 h after the injury around the needle tract and persisted throughout the experiment. Morphologically, these cells were thought to be mainly astrocytes.

Amyloid beta-Protein Precursor

Characterization of the human IL-5 receptors on eosinophils.

Interleukin 5 (IL-5) receptors on the cell surface of human eosinophils and other hematopoietic cells were characterized using radiolabeled recombinant IL-5. The binding of 35S-labeled murine IL-5 to eosinophils from normal human peripheral blood was rapid and saturable within a 30-min incubation at both 4 and 37 degrees C. The binding of 35S-labeled murine IL-5 to eosinophils was inhibited by an excess of unlabeled murine and human IL-5 or by an anti-murine IL-5 monoclonal antibody (NC17) but not by other human cytokines. Scatchard plot analysis revealed that human eosinophils have a single class of high affinity receptor (Kd 170-330 pM; number of binding sites: 260-380/cell). IL-5 receptors on eosinophils from four patients with eosinophilia displayed similar characteristics. Affinity cross-linking experiments resulted in the identification of human IL-5 receptor on eosinophils with a molecular mass of 55-60 kDa. Among the various cells besides eosinophils and cell lines that we could test, a subline of HL-60 (YY-1 cells) was found to display a significant number of IL-5 receptor. These results suggest that IL-5 may act on limited types of cells in the human system.

Aged